Pyrazoles, isoxazoles and pyrimidines of general formula I, II, III, and IV ##STR1## in which R.sup.1 represents COOH, COONa, COOR, CHO, C(OR).sub.2, CN, CONH.sub.2, CONHR or CONR.sub.2, in which R.sup.2 represents H, an alkyl-, cycloalkyl, aralkyl- or aryl-group with up to 12 carbon atoms, COOR, CONH.sub.2, CONHR, CONR.sub.2, alkyl-OH, cycloalkyl-OH, aralkyl-OH, aryl-OH, alkyl-OR, cycloalkyl-OR, aralkyl-OR and aryl-OR, in which R.sup.3 represents H, an alkyl-, cycloalkyl-, aralkyl- or aryl-group with up to 12 carbon atoms, OH, OR, SH, SR, NH.sub.2, NHR and NR.sub.2, NHNO.sub.2, NHNH.sub.2, NHNHR, NHNR.sub.2, COOR, CONH.sub.2, CONHR, CONR.sub.2, in which R.sup.4 represents an alkyl-, cycloalkyl-, aralkyl- or aryl-group with up to 12 carbon atoms are important intermediates in the manufacture of pharmaceuticals and agrochemicals. (R's independently of each other represent alkyl-, cycloalkyl, aryl-aralkyl-groups.)
The compounds of the present invention can be synthesized according to principally known procedures by condensing 2-substituted 1,3-dialdehydes of the general formula (V) ##STR2## in which R.sup.1 represents H, an alkyl-, cycloalkyl-, aralkyl-, aryl-group, COOH, COONa, COOR, CHO, C(OR).sub.2, CN, CONH.sub.2, CONHR or CONR.sub.2, with reagents such as hydroxylamines and their salts, hydrazines and their salts, formamid, amidines and their salts, guanidines and their salts, aminoguanidines and their salts, nitroguanidine and their salts, O-alkyl-isoureas and their salts, O-cycloalkyl-isoureas and their salts, O-aralkyl-isoureas and their salts, O-aryl-isoureas and their salts, S-alkyl-isothioureas, S-cycloalkyl-isothioureas, S-aralkyl-isothioureas, S-arylisothioureas, S-alkyl-isothiouronium salts, S-cycloalkyl-isothiouronium salts, S-aralkyl-isothiouronium salts, S-aryl-isothiuronium salts, thiourea and urea, respectively (JP 61,289,077; Schenone, P., Sansebastiano, L., Mosti, L., J. Heterocycl. Chem. 1990, 27 (2), 295; Holzer, W., Seiringer, G., J. Heterocycl. Chem. 1993, 30, 865; Kusumi, T. et al., Tetrahedron Letters 22 (1981), 36, 3451; Prelog, V., Wuersch, J., Koenigsbacher, K., Helv. Chim. Acta 1951, 34, 258; U.S. Pat. No. 4,808,595; Genin, M., J. et al. J. Med. Chem. 1998, 41; Reichardt, G., Kermer, W. D., Synthesis 1970, 538).
While the substituted malondialdehydes of general formula V normally are more stable toward polymerization than the unsubstituted malondialdehyde, they are thermally unstable as indicated, for example, by losses of 41% on distillation of ethoxycarbonyl-malondialdehyde under very mild conditions (Bertz, S. H., Dabbagh, G., Cotte, J. Org. Chem. 1982, 47, 2216). Handling-hazards and product losses, as well as a potential contamination of the reaction mixtures with polymeric material result from using the compounds of general formula II for the synthesis of heterocycles. Besides, the compounds of general formula I can be stored even above room temperature for extended periods of time.
Another disadvantage of synthesizing the compounds of general formula I, II, III and IV from the compounds of formula V is their limited availability. Production of the substituted aldehydes of general formula V from readily available starting materials generally requires several steps and the use of reagents that are difficult to handle under commercial conditions, such as NaH or CO. Besides, significant amounts of salt-waste are normally associated with the production of the compounds of general formula V. Consequently, a need existed for a process that allows for a production of the compounds of general formula I, II, III and IV from stable, easily available starting materials.